CN111714685A - Method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer - Google Patents
Method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer Download PDFInfo
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- CN111714685A CN111714685A CN202010700647.0A CN202010700647A CN111714685A CN 111714685 A CN111714685 A CN 111714685A CN 202010700647 A CN202010700647 A CN 202010700647A CN 111714685 A CN111714685 A CN 111714685A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
Abstract
The invention belongs to the field of biological materials, in particular to a method for preparing medical adhesive by using an alpha-alkyl cyanoacrylate monomer, formaldehyde, piperidine serving as a catalyst, sodium dodecyl sulfate, phosphoric acid serving as a basic catalyst, purified water, tricresyl phosphate serving as a plasticizer, hydroquinone serving as a polymerization inhibitor, ethyl cyanoacetate, isobutanol, phthalate and an acid catalyst, wherein the medical adhesive prepared by using the alpha-alkyl cyanoacrylate monomer, the formaldehyde, the piperidine serving as the catalyst, the phosphoric acid serving as the basic catalyst, the hydroquinone serving as the polymerization inhibitor and the acid catalyst can improve the compatibility of the medical; the invention is mainly used for solving the problems that the reaction speed of the reagents is low and the medical bonding capability is not strong due to poor compatibility among the reagents in the process of manufacturing the traditional medical adhesive, and simultaneously, the raw liquid in the three-neck flask is heated unevenly in the process of distilling and conducting heat to the three-neck flask by the methyl silicone oil because the methyl silicone oil in the oil pan is heated evenly, so that the raw liquid in the three-neck flask is layered.
Description
Technical Field
The invention belongs to the field of biological materials, and particularly relates to a method for preparing medical adhesive from an alpha-alkyl cyanoacrylate monomer.
Background
Three alpha-cyanoacrylate alkyl ester monomers, namely alpha-cyanoacrylate isobutyl, alpha-cyanoacrylate n-butyl and alpha-cyanoacrylate n-octyl, can react with a trace amount of water on the surface of the skin and anionic groups such as carbonyl [ OH ] and amino [ NH2 ] in body fluid due to the existence of two electron-withdrawing groups of cyano [ CN ] and carbonyl [ C ═ O ], can rapidly initiate the polymerization of the alpha-cyanoacrylate isobutyl monomer, and can form a protective film on the surface of the skin after 5 to 15 seconds, so that the skin can be tightly adhered, and tissues and bacteria can be isolated. The adhesive strength of the adhesive film is greater than the natural tension of the wound, so that the adhesive film can tightly adhere the skin and can play a role in immediately stopping bleeding and coagulating blood under the action of thrombin and fibrin; in biological evaluation, the cytotoxicity, intradermal reaction, skin sensitization, hemolysis, genetic toxicity, implantation and sub-chronic toxicity meet the requirements through tests, and in addition, the biological evaluation also has the characteristics of decomposition in vivo, excretion and the like; the excellent performance of the adhesive can lead other adhesive to be used for blood vessel adhesion, anastomotic adhesion of an intestinal canal and an esophagus, skin incision adhesion, sealing of exudates, repairing of defective tissues, sealing of fistula orificium, hemostasis in organ surgery and the like. For a description of the alkyl α -cyanoacrylate monomers, see journal: the synthesis and performance research of chestnut snow gorgeous and alpha-cyanoacrylate medical glue, university of southern China, 2013(15), but at present, the alpha-cyanoacrylate monomer still has some problems, and the method specifically comprises the following aspects:
the prior medical adhesive has the problems that the reaction speed of reagents is low and the medical adhesive capacity is not strong due to poor compatibility among the reagents in the manufacturing process, and meanwhile, in the process of distilling the stock solution in the three-neck flask, the stock solution in the three-neck flask is heated unevenly due to the fact that the methyl silicone oil in the oil pot is heated evenly, and the stock solution in the three-neck flask is heated unevenly during the process of distilling and conducting heat to the three-neck flask by the methyl silicone oil, so that the stock solution in the three-neck flask is layered.
In view of the above, in order to overcome the above technical problems, the present inventors designed and developed a method for preparing medical glue from an α -cyanoacrylate monomer, and made a special oil bath pan, thereby solving the above technical problems.
Disclosure of Invention
In order to make up for the defects of the prior art, the invention aims to provide a method for preparing medical glue by using an alpha-alkyl cyanoacrylate monomer, which is mainly used for solving the problems that the compatibility among reagents is poor in the process of preparing the conventional medical glue, thereby leading to slower reaction speed of the reagent and weak medical bonding capability, and simultaneously, in the process of distilling the stock solution in the three-neck flask, because the methyl silicone oil in the oil pan is uniformly heated, the stock solution in the three-neck flask can be heated unevenly in the process of distilling and conducting heat to the three-neck flask by the methyl silicone oil, so that the stock solution in the three-neck flask can be layered, the delamination of the stock solution reduces the reaction rate of the various reagents in the stock solution, which in turn reduces the process problems of the exchange reaction of the alkyl- α -cyanoacrylate.
The technical scheme adopted by the invention for solving the technical problems is as follows: the invention relates to a method for preparing medical adhesive by alpha-alkyl cyanoacrylate monomer; the medical adhesive is prepared from the following raw materials:
25-30 parts of alpha-alkyl cyanoacrylate monomer, 15-20 parts of formaldehyde, 8-10 parts of catalyst piperidine, 6-8 parts of sodium dodecyl sulfate, 4-6 parts of alkaline catalyst phosphoric acid, 15-20 parts of purified water, 4-6 parts of plasticizer tricresyl phosphate, 2-5 parts of polymerization inhibitor hydroquinone, 15-18 parts of ethyl cyanoacetate, 10-15 parts of isobutanol, 3-5 parts of phthalate and 6-8 parts of acid catalyst;
the method comprises the following steps:
s1: putting sodium dodecyl sulfate in raw materials into a reaction kettle filled with purified water, then putting alpha-alkyl cyanoacrylate monomer in the raw materials into the reaction kettle, heating to 40-60 ℃, dropping piperidine in the raw materials into the reaction kettle when the temperature of the reaction kettle reaches 45-50 ℃, and quickly stirring for reaction to obtain an alpha-alkyl cyanoacrylate monomer condensation compound after the reaction of the raw materials is finished;
s2: mixing the alpha-alkyl cyanoacrylate monomer condensate prepared in S1 with phosphoric acid, tricresyl phosphate as a plasticizer and hydroquinone as a polymerization inhibitor in the raw materials in a ratio of 1:2:1:0.5:0.3 in a three-neck flask, then putting the three-neck flask in an oil bath environment for depolymerization reaction for 3-4 hours, and finishing the purification of the alpha-alkyl cyanoacrylate monomer after the depolymerization reaction is finished;
s3: sequentially placing the alpha-alkyl cyanoacrylate monomer purified in the S2, ethyl cyanoacetate and isobutanol into a three-neck flask, then placing the three-neck flask into an oil bath pot, continuously heating the oil bath pot, increasing the temperature by 10 ℃ per minute, and obtaining crude ester after the three-neck flask is heated due to the fact that the highest heating temperature is 140-160 ℃;
s4: dripping an acid catalyst into the continuous phase flask in the process of heating the flask in S3, wherein the reaction process of the ester exchange reaction can be promoted in the process;
s5: sequentially putting phthalate, polycaprolactone and polymethacrylate in the raw materials into a flask for preparing crude ester, heating the flask, carrying out depolymerization reaction on a reagent in the flask during the heating of the flask, continuously adding tricresyl phosphate, phosphoric acid and an acidic catalyst into the flask for carrying out depolymerization reaction after the depolymerization reaction in the flask is finished, and taking out the reagent after the depolymerization reaction in the flask is finished to obtain the medical adhesive;
wherein, the oil bath pan comprises a base and an oil pan; the oil pan is arranged on the upper surface of the base; methyl silicone oil is filled in the oil pan; the cavity in the oil pan is fixedly connected with a support ring on the end surface of the bottom of the oil pan; first through holes are uniformly distributed in the inner wall of the support ring and are communicated with the support ring; the end surface of the top of the supporting ring is fixedly connected with a supporting plate; the inner wall of the supporting plate is provided with a bidirectional electric telescopic rod, and the electric telescopic rod is electrically connected with the controller through a lead; the driving shaft below the electric telescopic rod extends into the supporting ring cavity; a first pressing plate is connected in the cavity of the supporting ring in a sliding manner and is fixedly connected with an expansion shaft below the electric telescopic rod; second through holes which are uniformly distributed are formed in the inner wall of the first pressing plate; an oil bath bin is fixedly connected above the supporting plate through uniformly arranged supporting blocks, and a three-neck flask is placed in the oil bath bin; an arc-shaped groove is formed in the inner wall of the oil bath bin, and third through holes which are uniformly distributed are formed in the inner wall of the arc-shaped groove; the inner wall of the arc-shaped groove is fixedly connected with uniformly arranged hoses; each hose part extends into the first pressing plate and penetrates through the first pressing plate; each hose portion extends into the support plate and is designed to penetrate through the support plate; the outer surface of the support ring is fixedly connected with guide pipes which are uniformly arranged, and the other ends of the guide pipes extend into the oil bath bin; the bottom end face of the three-mouth flask is fixedly connected with an extrusion bin, and extrusion holes which are uniformly distributed are formed in the inner wall of the extrusion bin; the cavity of the extrusion bin is internally and slidably connected with an extrusion plate; the lower surface of the extrusion plate is fixedly connected with a driving rod, and the driving rod extends out of the three-neck flask and is clamped with a driving shaft above the electric telescopic rod;
when the oil bath kettle works, in the process of distilling the stock solution in the three-neck flask, because the methyl silicone oil in the oil bath kettle is uniformly heated, the stock solution in the three-neck flask can be heated unevenly in the process of distilling and conducting heat to the three-neck flask by the methyl silicone oil, so that the stock solution in the three-neck flask can be layered, the reaction speed of various reagents in the stock solution can be reduced due to the layering of the stock solution, and the exchange reaction process of alpha-alkyl cyanoacrylate is further reduced. When the oil bath pan manufactured by the invention is used, firstly, the three-neck flask is placed in the oil bath bin, the driving rod in the three-neck flask is clamped on the driving shaft above the electric telescopic rod, the methyl silicone oil is added into the oil bath pan, then the oil bath pan is started, after the oil bath pan is started, the oil bath pan heats the methyl silicone oil, the controller controls the electric telescopic rod to stretch up and down, the first pressing plate can be pushed to move downwards in the downward stretching process of the electric telescopic rod, the oil in the oil bath pan can be diffused in the process, so that the methyl silicone oil is heated uniformly, meanwhile, the oil below the first pressing plate can be pressed into the arc-shaped groove through the hose, the oil flowing into the arc-shaped groove is sprayed on the outer surface of the three-neck flask through the third through the uniformly arranged through holes, the three-neck flask can be heated uniformly in the process, so that the phenomenon of layering of the raw liquid in the three-neck flask is, meanwhile, the oil in the supporting ring can be pressed into the oil bath bin through the uniformly arranged guide pipes, the three-mouth flask can be further conducted with heat in the process, when the electric telescopic rod stretches upwards, the electric telescopic rod drives the first pressing plate to move upwards, the oil flowing into the upper part of the first pressing plate through the second through hole can be pressed into the arc-shaped groove through the hose in the process, the stock solution can be further uniformly heated in the process, meanwhile, the oil in the oil pot can be stirred, so that the oil is uniformly heated, in the process of stretching upwards through the electric telescopic rod, the driving rod is clamped with the electric telescopic rod, so that the extrusion plate can be pushed to move upwards through the driving rod, the stock solution flowing into the extrusion bin can be extruded out through the uniformly arranged extrusion holes in the process, and the stock solution in the three-mouth flask can be stirred in the process, therefore, the stock solution is heated uniformly, meanwhile, the stock solution can be prevented from being heated unevenly to cause stock solution layering, the exchange reaction of the alpha-alkyl cyanoacrylate is promoted to be slow, and the stock solution can be pumped into the extrusion bin through the extrusion holes in the process that the extrusion plate moves downwards so as to circulate.
Preferably, an arc-shaped bag is fixedly connected to the inner surface of the oil bath bin in the cavity of the oil bath bin, and the arc-shaped bag is made of a heat-conducting silica gel material; the third through hole of the arc-shaped capsule wrapping part is designed; uniformly arranged spray holes are formed in the inner wall of the arc-shaped bag;
when the three-mouth flask is in work, because the arc-shaped layer fixedly connected with the inner surface of the oil bath bin is partially wrapped with the third through hole, the oil flowing out of the third through hole can flow into the arc-shaped bag, and can expand when the oil in the arc-shaped bag increases, and can be attached to the outer surface of the three-mouth flask after the arc-shaped bag expands, so that the three-mouth flask can be uniformly heated in the process, and simultaneously, the three-mouth flask is matched with the diffusion of the stock solution in the three-mouth flask, so that the stock solution can be better uniformly heated, and further, the exchange reaction process of the alpha-alkyl cyanoacrylate is improved, because the arc-shaped bag is made of heat-conducting silica gel material, and the heat-conducting silica gel has stronger heat-conducting capacity, the heat-conducting effect on the three-mouth flask can be improved, and simultaneously, the inclination of the three-mouth flask can also, in the process, the oil can flow in the oil bath bin, so that the oil is prevented from being stored in the oil bath bin for a long time, and the heat conduction effect of the three-neck flask is prevented from being influenced.
Preferably, the outer surface of the extrusion bin is fixedly connected with first bent pipes which are uniformly arranged, and the first bent pipes are communicated with the extrusion bin; the upper surface of the extrusion plate is rotatably connected with a rotating blade through a long rod, and the rotating blade extends to the upper part of the extrusion bin; the rotating blade and the first bent pipe part correspond to each other;
when in work, as the first bent pipes which are uniformly arranged are fixedly connected to the outer surface of the extrusion bin, the stock solution can be extruded out through the first bent pipes in the upward movement process of the extrusion plate, in the process, the flowing degree of the stock solution can be increased, so that the stock solution can circularly flow in the three-neck flask, in the process, the heating degree of the stock solution can be improved, so that the stock solution is prevented from being layered, and meanwhile, the exchange reaction process of the alpha-alkyl cyanoacrylate can be accelerated, because the first bent pipe and the rotating blade are mutually corresponding, the stock solutions can be mixed in the liquid spraying process of the first bent pipe, so that the exchange reaction process of the alpha-alkyl cyanoacrylate can be further improved, the rotating blade can be pushed to rotate at the same time, the circulation between stock solutions can be promoted in the rotating process of the rotating vane, so that the exchange reaction process of the alpha-cyanoacrylate alkyl ester is further improved.
Preferably, the raw materials also comprise polycaprolactone and polymethacrylate;
the polycaprolactone is a high molecular organic polymer which is prepared by ring opening polymerization of caprolactone monomers under the catalysis of a metal anion complex catalyst, the compatibility among raw materials can be improved by using the polycaprolactone-based medical adhesive in the invention, so that the depolymerization reaction in a reagent can be improved, the toxicity and the hemolysis rate of cells can be reduced by using the polycaprolactone-based medical adhesive, the polymethacrylate in the raw materials is a general name of homopolymer and copolymer of methacrylate, the adhesive strength of the medical adhesive can be improved by using the polycaprolactone-based medical adhesive in the invention, and the medical adhesive can be prevented from being poor in viscosity and easy to fall off.
Preferably, the acid catalyst is a mixture of concentrated sulfuric acid and sulfonic acid, and the catalyst does not contain moisture;
because the acid catalyst is a mixture of sulfuric acid and sulfonic acid, when the acid catalyst is added into the flask, the sulfuric acid and the sulfonic acid can absorb moisture in the flask, so that the transesterification efficiency of the reagent can be improved, the water content in the reagent can be reduced, the phenomenon that water is layered in the reagent to influence the transesterification conversion rate can be prevented, free acid radicals can be combined with alcohol in the reagent, the transesterification reaction rate can be further improved, and because the catalyst does not contain moisture, the transesterification conversion rate can be reduced if the catalyst contains moisture, so that the exchange degree of the whole reagent is reduced.
Preferably, the catalyst also contains liquid chlorine, and the content of the liquid chlorine is one tenth of the total amount of the catalyst;
because the catalyst contains liquid chlorine, when the liquid chlorine enters the flask, the liquid chlorine can react with water in the flask to generate hydrogen chloride and chloric acid, and water in the reagent can be further absorbed in the process, so that the conversion rate of transesterification of the reagent can be further improved, and meanwhile, the generated hydrogen chloride and chloric acid can catalyze the reagent, so that the conversion rate of transesterification of the reagent can be further improved.
The invention has the following beneficial effects:
1. according to the invention, by adding the acid catalyst, the acid catalyst is a mixture of sulfuric acid and sulfonic acid, when the acid catalyst is added into the flask, the sulfuric acid and the sulfonic acid can absorb moisture in the flask, so that the transesterification efficiency of the reagent can be improved, and simultaneously the water content in the reagent can be reduced, so that the water can be prevented from being layered in the reagent to influence the transesterification conversion rate, and simultaneously the free acid radicals can be combined with alcohol in the reagent, so that the transesterification reaction rate can be further improved.
2. The invention has the advantages that the arc-shaped bag is arranged, the oil in the arc-shaped bag expands when increasing, the arc-shaped bag can be attached to the outer surface of the three-neck flask after expanding, in the process, the three-mouth flask can be heated uniformly, and simultaneously the stock solution is matched to be diffused in the three-mouth flask, thereby the stock solution can be heated evenly better, and the exchange reaction process of the alpha-cyanoacrylate is further improved, because the arc-shaped capsule is made of heat-conducting silica gel material and the heat-conducting silica gel has stronger heat-conducting capability, the heat-conducting effect on the three-mouth flask can be improved, meanwhile, the three-mouth flask can be prevented from inclining, because the inner wall of the arc-shaped bag is provided with the nozzle, the oil in the arc-shaped bag can flow into the outer surface of the three-mouth flask through the nozzle, in the process, the oil can flow in the oil bath bin, so that the oil is prevented from being stored in the oil bath bin for a long time, and the heat conduction effect of the three-neck flask is prevented from being influenced.
Drawings
The invention will be further explained with reference to the drawings.
FIG. 1 is a flow chart of the method of the present invention;
FIG. 2 is a front view of the oil bath pan of the present invention;
FIG. 3 is a cross-sectional view of an oil bath pan of the present invention;
FIG. 4 is an enlarged view of a portion of FIG. 3 at A;
FIG. 5 is a partial enlarged view at B in FIG. 3;
in the figure: the oil pan comprises an oil pan 1, a support ring 11, a first through hole 12, a support plate 13, an electric telescopic rod 14, a first pressure plate 15, a second through hole 16, a hose 17, a conduit 18, an oil bath bin 2, a three-neck flask 21, an arc-shaped groove 22, a third through hole 23, an extrusion bin 24, an extrusion hole 25, an extrusion plate 26, an arc-shaped bag 27, a spray hole 28, a first elbow 29 and a rotary vane 191.
Detailed Description
A method for preparing a medical adhesive using an α -cyanoacrylate monomer according to an embodiment of the present invention will be described below with reference to fig. 1 to 5.
As shown in fig. 1 to 5, the method for preparing medical adhesive by using the alpha-alkyl cyanoacrylate monomer of the invention; the medical adhesive is prepared from the following raw materials:
25-30 parts of alpha-alkyl cyanoacrylate monomer, 15-20 parts of formaldehyde, 8-10 parts of catalyst piperidine, 6-8 parts of sodium dodecyl sulfate, 4-6 parts of alkaline catalyst phosphoric acid, 15-20 parts of purified water, 4-6 parts of plasticizer tricresyl phosphate, 2-5 parts of polymerization inhibitor hydroquinone, 15-18 parts of ethyl cyanoacetate, 10-15 parts of isobutanol, 3-5 parts of phthalate and 6-8 parts of acid catalyst;
the method comprises the following steps:
s1: putting sodium dodecyl sulfate in raw materials into a reaction kettle filled with purified water, then putting alpha-alkyl cyanoacrylate monomer in the raw materials into the reaction kettle, heating to 40-60 ℃, dropping piperidine in the raw materials into the reaction kettle when the temperature of the reaction kettle reaches 45-50 ℃, and quickly stirring for reaction to obtain an alpha-alkyl cyanoacrylate monomer condensation compound after the reaction of the raw materials is finished;
s2: mixing the alpha-alkyl cyanoacrylate monomer condensate prepared in S1 with phosphoric acid, tricresyl phosphate as a plasticizer and hydroquinone as a polymerization inhibitor in the raw materials in a ratio of 1:2:1:0.5:0.3 in a three-neck flask, then putting the three-neck flask in an oil bath environment for depolymerization reaction for 3-4 hours, and finishing the purification of the alpha-alkyl cyanoacrylate monomer after the depolymerization reaction is finished;
s3: sequentially placing the alpha-alkyl cyanoacrylate monomer purified in the S2, ethyl cyanoacetate and isobutanol into a three-neck flask, then placing the three-neck flask into an oil bath pot, continuously heating the oil bath pot, increasing the temperature by 10 ℃ per minute, and obtaining crude ester after the three-neck flask is heated due to the fact that the highest heating temperature is 140-160 ℃;
s4: dripping an acid catalyst into the continuous phase flask in the process of heating the flask in S3, wherein the reaction process of the ester exchange reaction can be promoted in the process;
s5: sequentially putting phthalate, polycaprolactone and polymethacrylate in the raw materials into a flask for preparing crude ester, heating the flask, carrying out depolymerization reaction on a reagent in the flask during the heating of the flask, continuously adding tricresyl phosphate, phosphoric acid and an acidic catalyst into the flask for carrying out depolymerization reaction after the depolymerization reaction in the flask is finished, and taking out the reagent after the depolymerization reaction in the flask is finished to obtain the medical adhesive;
wherein, the oil bath pan comprises a base and an oil pan 1; the oil pan 1 is arranged on the upper surface of the base; methyl silicone oil is contained in the oil pan 1; the cavity in the oil pan 1 is fixedly connected with a support ring 11 on the end face of the bottom of the oil pan 1; first through holes 12 are uniformly distributed in the inner wall of the support ring 11, and the first through holes 12 are communicated with the support ring 11; the top end face of the support ring 11 is fixedly connected with a support plate 13; a bidirectional electric telescopic rod 14 is arranged in the inner wall of the supporting plate 13, and the electric telescopic rod 14 is electrically connected with the controller through a lead; the driving shaft below the electric telescopic rod 14 extends into the cavity of the supporting ring 11; a first pressure plate 15 is connected in the cavity of the support ring 11 in a sliding manner, and the first pressure plate 15 is fixedly connected with a telescopic shaft below the electric telescopic rod 14; second through holes 16 which are uniformly distributed are formed in the inner wall of the first pressing plate 15; an oil bath bin 2 is fixedly connected above the supporting plate 13 through uniformly arranged supporting blocks, and a three-neck flask 21 is placed in the oil bath bin 2; an arc-shaped groove 22 is formed in the inner wall of the oil bath bin 2, and third through holes 23 which are uniformly distributed are formed in the inner wall of the arc-shaped groove 22; the inner wall of the arc-shaped groove 22 is fixedly connected with uniformly arranged hoses 17; each of said flexible tubes 17 extends partly inside the first pressure plate 15 and is designed to extend through the first pressure plate 15; each of said hose portions 17 extends into the support plate 13 and is designed to penetrate the support plate 13; the outer surface of the support ring 11 is fixedly connected with guide pipes 18 which are uniformly arranged, and the other ends of the guide pipes 18 extend into the oil bath bin 2; the bottom end face of the three-mouth flask 21 is fixedly connected with an extrusion bin 24, and extrusion holes 25 which are uniformly distributed are formed in the inner wall of the extrusion bin 24; an extrusion plate 26 is connected in the cavity of the extrusion bin 24 in a sliding manner; the lower surface of the extrusion plate 26 is fixedly connected with a driving rod, and the driving rod extends out of the three-neck flask 21 and is clamped with a driving shaft above the electric telescopic rod 14;
when the three-neck flask is in operation, in the process of distilling the stock solution in the three-neck flask 21, because the methyl silicone oil in the oil pan 1 is uniformly heated, the stock solution in the three-neck flask 21 is heated unevenly in the process of distilling and conducting heat to the three-neck flask 21 by the methyl silicone oil, so that the stock solution in the three-neck flask 21 is layered, and because the stock solution is layered, the reaction speed of various reagents in the stock solution can be reduced, and further the exchange reaction process of the alpha-alkyl cyanoacrylate is reduced, the oil bath pan manufactured by the invention can uniformly heat the methyl silicone oil in the oil pan 1, and simultaneously can uniformly introduce the methyl silicone into the oil bath bin 2, so that the methyl silicone can be in all-dimensional contact with the three-neck flask 21 for conducting heat, and simultaneously can push the stock solution in the three-neck flask 21 to circulate, thereby uniformly heating the stock solution, when the oil bath pot manufactured by the invention is used, firstly the three-neck flask 21 is placed into the oil bath bin 2, meanwhile, the driving rod in the three-neck flask 21 is clamped on the driving shaft above the electric telescopic rod 14, the methyl silicone oil is added into the oil bath pot 1 at the moment, then the oil bath pot is started, after the oil bath pot is started, the methyl silicone oil is heated by the oil bath pot 1 at the moment, the controller controls the electric telescopic rod 14 to stretch up and down at the moment, the first pressing plate 15 can be pushed to move downwards in the downward stretching process of the electric telescopic rod 14, the oil in the oil bath pot 1 can be diffused in the process, so that the methyl silicone oil is heated uniformly, meanwhile, the hose 17 below the first pressing plate 15 can be pressed into the arc-shaped groove 22 through the hose 17, at the moment, the oil flowing into the arc-shaped groove 22 is sprayed on the outer surface of the three-neck flask 21 through the uniformly arranged third through holes 23, in the process, the three-neck flask 21 can be heated uniformly, so that the phenomenon of layering of raw liquid in the three-neck flask 21 is prevented, meanwhile, oil in the support ring 11 can be pressed into the oil bath bin 2 through the guide pipes 18 which are uniformly arranged, the three-neck flask 21 can be further conducted with heat, when the electric telescopic rod 14 stretches upwards, the electric telescopic rod 14 drives the first pressing plate 15 to move upwards, in the process, the oil flowing into the upper part of the first pressing plate 15 through the second through hole 16 can be pressed into the arc-shaped groove 22 through the hose 17, in the process, the raw liquid can be further heated uniformly, and simultaneously, the oil in the oil bath 1 can be stirred, so that the oil is heated uniformly, in the process that the electric telescopic rod 14 stretches upwards, because the driving rod is clamped with the electric telescopic rod 14, the extrusion plate 26 can be pushed to move upwards through the driving rod, in the process, the stock solution flowing into the extrusion bin 24 can be extruded out by the extrusion plate 26 through the extrusion holes 25 which are uniformly arranged, the stock solution in the three-neck flask 21 can be stirred in the process, so that the stock solution is uniformly heated, meanwhile, the stock solution can be prevented from being layered due to nonuniform heating, the exchange reaction of the alpha-alkyl cyanoacrylate is promoted to be slow, and the stock solution can be pumped into the extrusion bin 24 through the extrusion holes 25 in the downward moving process of the extrusion plate 26, so that the circulation is realized.
As an embodiment of the invention, an arc-shaped bag 27 is fixedly connected to the inner surface of the oil bath bin 2 in the cavity of the oil bath bin 2, and the arc-shaped bag 27 is made of a heat-conducting silica gel material; the arc-shaped bag 27 wraps part of the third through hole 23; uniformly arranged spray holes 28 are formed in the inner wall of the arc-shaped bag 27;
when the three-mouth flask is in operation, because the arc-shaped layer fixedly connected with the inner surface of the oil bath bin 2 is partially wrapped by the third through hole 23, the oil flowing out of the third through hole 23 can flow into the arc-shaped bag 27, and expands when the oil in the arc-shaped bag 27 increases, and the expanded arc-shaped bag 27 can be attached to the outer surface of the three-mouth flask 21, so that the three-mouth flask 21 can be heated uniformly in the process, and the original liquid can be matched with the diffusion of the original liquid in the three-mouth flask 21, thereby better enabling the original liquid to be heated uniformly, further improving the exchange reaction process of the alpha-alkyl cyanoacrylate, because the arc-shaped bag 27 is made of heat-conducting silica gel material and the heat-conducting silica gel has stronger heat-conducting capacity, the heat-conducting effect on the three-mouth flask 21 can be improved, meanwhile, the three-mouth flask can be prevented from inclining, because a nozzle is arranged in the inner wall of the arc-shaped, in the process, the oil can flow in the oil bath bin 2, so that the oil is prevented from being stored in the oil bath bin 2 for a long time and the heat conduction effect of the three-neck flask 21 is prevented from being influenced.
As an embodiment of the invention, the outer surface of the extrusion bin 24 is fixedly connected with first bent pipes 29 which are uniformly arranged, and the first bent pipes 29 are communicated with the extrusion bin 24; the upper surface of the extrusion plate 26 is rotatably connected with a rotating vane 291 through a long rod, and the rotating vane 291 extends above the extrusion bin 24; the rotating blade 291 and the first bent pipe 29 correspond to each other in part;
when in work, as the first bent pipes 29 which are uniformly arranged are fixedly connected to the outer surface of the extrusion bin 24, the stock solution can be extruded out through the first bent pipes 29 in the process that the extrusion plate 26 moves upwards, in the process, the flowing degree of the stock solution can be increased, so that the stock solution can circularly flow in the three-neck flask 21, in the process, the heating degree of the stock solution can be improved, so that the stock solution is prevented from being layered, and meanwhile, the exchange reaction process of the alpha-alkyl cyanoacrylate can be accelerated, because the first bent pipe 29 and the rotating blade 291 correspond to each other, the stock solutions can be mixed during the liquid spraying process of the first bend 29, so that the exchange reaction process of the alpha-alkyl cyanoacrylate can be further improved, and the rotating blade 291 can be pushed to rotate, circulation between the stock solutions is also promoted during the rotation of the rotating blade 291, thereby further improving the exchange reaction process of the alpha-cyanoacrylate.
As an embodiment of the invention, the raw materials further comprise polycaprolactone and polymethacrylate;
the polycaprolactone is a high molecular organic polymer which is prepared by ring opening polymerization of caprolactone monomers under the catalysis of a metal anion complex catalyst, the compatibility among raw materials can be improved by using the polycaprolactone-based medical adhesive in the invention, so that the depolymerization reaction in a reagent can be improved, the toxicity and the hemolysis rate of cells can be reduced by using the polycaprolactone-based medical adhesive, the polymethacrylate in the raw materials is a general name of homopolymer and copolymer of methacrylate, the adhesive strength of the medical adhesive can be improved by using the polycaprolactone-based medical adhesive in the invention, and the medical adhesive can be prevented from being poor in viscosity and easy to fall off.
In one embodiment of the present invention, the acidic catalyst is a mixture of concentrated sulfuric acid and sulfonic acid, and the catalyst does not contain moisture;
because the acid catalyst is a mixture of sulfuric acid and sulfonic acid, when the acid catalyst is added into the flask, the sulfuric acid and the sulfonic acid can absorb moisture in the flask, so that the transesterification efficiency of the reagent can be improved, the water content in the reagent can be reduced, the phenomenon that water is layered in the reagent to influence the transesterification conversion rate can be prevented, free acid radicals can be combined with alcohol in the reagent, the transesterification reaction rate can be further improved, and because the catalyst does not contain moisture, the transesterification conversion rate can be reduced if the catalyst contains moisture, so that the exchange degree of the whole reagent is reduced.
In one embodiment of the invention, the catalyst also contains liquid chlorine, and the content of the liquid chlorine is one tenth of the total amount of the catalyst;
because the catalyst contains liquid chlorine, when the liquid chlorine enters the flask, the liquid chlorine can react with water in the flask to generate hydrogen chloride and chloric acid, and water in the reagent can be further absorbed in the process, so that the conversion rate of transesterification of the reagent can be further improved, and meanwhile, the generated hydrogen chloride and chloric acid can catalyze the reagent, so that the conversion rate of transesterification of the reagent can be further improved.
The specific working process is as follows:
when the oil bath pot manufactured by the invention is used, firstly the three-neck flask 21 is placed into the oil bath bin 2, the driving rod in the three-neck flask 21 is clamped on the driving shaft above the electric telescopic rod 14, the methyl silicone oil is added into the oil pot 1 at the moment, then the oil bath pot is started, after the oil bath pot is started, the methyl silicone oil is heated by the oil pot 1 at the moment, the controller controls the electric telescopic rod 14 to stretch up and down at the moment, the first pressing plate 15 can be pushed to move downwards in the process that the electric telescopic rod 14 stretches up downwards, the oil in the oil pot 1 can be diffused in the process, so that the methyl silicone oil is heated uniformly, meanwhile, the part below the first pressing plate 15 can be pressed into the arc-shaped groove 22 through the hose 17, the oil flowing into the arc-shaped groove 22 is sprayed on the outer surface of the three-neck flask 21 through the third through holes 23 which are uniformly arranged, so that the three-neck flask 21 can be heated uniformly in the process, therefore, the phenomenon of layering of the stock solution in the three-neck flask 21 is prevented, meanwhile, the oil in the support ring 11 can be pressed into the oil bath bin 2 through the uniformly arranged guide pipes 18, the three-neck flask 21 can be further conducted with heat conduction in the process, when the electric telescopic rod 14 is stretched upwards, the electric telescopic rod 14 drives the first pressing plate 15 to move upwards, the oil flowing into the upper part of the first pressing plate 15 through the second through hole 16 can be pressed into the arc-shaped groove 22 through the hose 17 in the process, the stock solution can be further uniformly heated in the process, meanwhile, the oil in the oil bath 1 can be stirred, so that the oil is uniformly heated, in the process that the electric telescopic rod 14 is stretched upwards, the driving rod is clamped with the electric telescopic rod 14, so that the extrusion plate 26 can be pushed to move upwards through the driving rod, and in the process, the extrusion plate 26 can extrude the stock solution flowing into the extrusion bin 24 through the uniformly arranged extrusion holes 25, in the process, the stock solution in the three-neck flask 21 can be stirred, so that the stock solution is heated uniformly, meanwhile, the stock solution can be prevented from being heated non-uniformly to cause layering of the stock solution, the exchange reaction of the alpha-alkyl cyanoacrylate is promoted to be slow, and the stock solution can be pumped into the extrusion bin 24 through the extrusion holes 25 in the process that the extrusion plate 26 moves downwards, so that the circulation is realized.
The foregoing illustrates and describes the principles, general features, and advantages of the present invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (6)
1. A method for preparing medical glue by using alpha-alkyl cyanoacrylate monomer is characterized in that: the medical adhesive is prepared from the following raw materials:
25-30 parts of alpha-alkyl cyanoacrylate monomer, 15-20 parts of formaldehyde, 8-10 parts of catalyst piperidine, 6-8 parts of sodium dodecyl sulfate, 4-6 parts of alkaline catalyst phosphoric acid, 15-20 parts of purified water, 4-6 parts of plasticizer tricresyl phosphate, 2-5 parts of polymerization inhibitor hydroquinone, 15-18 parts of ethyl cyanoacetate, 10-15 parts of isobutanol, 3-5 parts of phthalate and 6-8 parts of acid catalyst;
the method comprises the following steps:
s1: putting sodium dodecyl sulfate in raw materials into a reaction kettle filled with purified water, then putting alpha-alkyl cyanoacrylate monomer in the raw materials into the reaction kettle, heating to 40-60 ℃, dropping piperidine in the raw materials into the reaction kettle when the temperature of the reaction kettle reaches 45-50 ℃, and quickly stirring for reaction to obtain an alpha-alkyl cyanoacrylate monomer condensation compound after the reaction of the raw materials is finished;
s2: mixing the alpha-alkyl cyanoacrylate monomer condensate prepared in S1 with phosphoric acid, tricresyl phosphate as a plasticizer and hydroquinone as a polymerization inhibitor in the raw materials in a ratio of 1:2:1:0.5:0.3 in a three-neck flask, then putting the three-neck flask in an oil bath environment for depolymerization reaction for 3-4 hours, and finishing the purification of the alpha-alkyl cyanoacrylate monomer after the depolymerization reaction is finished;
s3: sequentially placing the alpha-alkyl cyanoacrylate monomer purified in the S2, ethyl cyanoacetate and isobutanol into a three-neck flask, then placing the three-neck flask into an oil bath pot, continuously heating the oil bath pot, increasing the temperature by 10 ℃ per minute, and obtaining crude ester after the three-neck flask is heated due to the fact that the highest heating temperature is 140-160 ℃;
s4: dripping an acid catalyst into the continuous phase flask in the process of heating the flask in S3, wherein the reaction process of the ester exchange reaction can be promoted in the process;
s5: sequentially putting phthalate, polycaprolactone and polymethacrylate in the raw materials into a flask for preparing crude ester, heating the flask, carrying out depolymerization reaction on a reagent in the flask during the heating of the flask, continuously adding tricresyl phosphate, phosphoric acid and an acidic catalyst into the flask for carrying out depolymerization reaction after the depolymerization reaction in the flask is finished, and taking out the reagent after the depolymerization reaction in the flask is finished to obtain the medical adhesive;
wherein, the oil bath pan comprises a base and an oil pan (1); the oil pan (1) is arranged on the upper surface of the base; methyl silicone oil is contained in the oil pan (1); the cavity in the oil pan (1) is fixedly connected with a support ring (11) on the end face of the bottom of the oil pan (1); first through holes (12) which are uniformly distributed are formed in the inner wall of the support ring (11), and the first through holes (12) are communicated with the support ring (11); the top end face of the support ring (11) is fixedly connected with a support plate (13); a bidirectional electric telescopic rod (14) is arranged in the inner wall of the supporting plate (13), and the electric telescopic rod (14) is electrically connected with the controller through a lead; a driving shaft below the electric telescopic rod (14) extends into the cavity of the supporting ring (11); a first pressure plate (15) is connected in the cavity of the support ring (11) in a sliding manner, and the first pressure plate (15) is fixedly connected with a telescopic shaft below the electric telescopic rod (14); second through holes (16) which are uniformly distributed are formed in the inner wall of the first pressing plate (15); an oil bath bin (2) is fixedly connected above the supporting plate (13) through uniformly arranged supporting blocks, and a three-neck flask (21) is placed in the oil bath bin (2); an arc-shaped groove (22) is formed in the inner wall of the oil bath bin (2), and third through holes (23) which are uniformly distributed are formed in the inner wall of the arc-shaped groove (22); the inner wall of the arc-shaped groove (22) is fixedly connected with uniformly arranged hoses (17); each hose (17) extends partially into the first pressure plate (15) and is designed to penetrate through the first pressure plate (15); each hose (17) portion extends into the support plate (13) and is designed to penetrate through the support plate (13); the outer surface of the support ring (11) is fixedly connected with guide pipes (18) which are uniformly arranged, and the other ends of the guide pipes (18) extend into the oil bath bin (2); the bottom end face of the three-mouth flask (21) is fixedly connected with an extrusion bin (24), and extrusion holes (25) which are uniformly distributed are formed in the inner wall of the extrusion bin (24); an extrusion plate (26) is connected in the cavity of the extrusion bin (24) in a sliding way; the lower surface of the extrusion plate (26) is fixedly connected with a driving rod, and the driving rod extends out of the design of the three-neck flask (21) and is connected with a driving shaft above the electric telescopic rod (14) in a clamping mode.
2. The method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer according to claim 1, wherein: an arc-shaped bag (27) is fixedly connected to the inner surface of the oil bath bin (2) in the cavity of the oil bath bin (2), and the arc-shaped bag (27) is made of a heat-conducting silica gel material; the arc-shaped bag (27) wraps part of the third through hole (23); the inner wall of the arc-shaped bag (27) is provided with evenly distributed spray holes (28).
3. The method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer according to claim 1, wherein: the outer surface of the extrusion bin (24) is fixedly connected with first bent pipes (29) which are uniformly arranged, and the first bent pipes (29) are communicated with the extrusion bin (24); the upper surface of the extrusion plate (26) is rotatably connected with a rotating blade (291) through a long rod, and the rotating blade (291) extends above the extrusion bin (24); the rotating blade (291) and the first bent pipe (29) are partially corresponding to each other.
4. The method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer according to claim 1, wherein: the raw materials also comprise polycaprolactone and polymethacrylate.
5. The method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer according to claim 1, wherein: the acid catalyst is a mixture of concentrated sulfuric acid and sulfonic acid, and the catalyst does not contain moisture.
6. The method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer according to claim 5, wherein: the catalyst also contains liquid chlorine, and the content of the liquid chlorine is one tenth of the total amount of the catalyst.
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| CN202010700647.0A CN111714685A (en) | 2020-07-20 | 2020-07-20 | Method for preparing medical adhesive from alpha-alkyl cyanoacrylate monomer |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796591A (en) * | 2022-06-06 | 2022-07-29 | 北京康派特医疗器械有限公司 | Cyanoacrylate medical adhesive and preparation method and application thereof |
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| CN101468212A (en) * | 2008-05-05 | 2009-07-01 | 孙丽华 | Preparation and application of isobutylcyanoacrylate medical adhesive |
| CN205649337U (en) * | 2016-03-14 | 2016-10-19 | 天津金世制药有限公司 | Oil bath heating intermediate layer pot |
| CN109748819A (en) * | 2019-02-28 | 2019-05-14 | 秦皇岛市科峰医疗器械有限公司 | The preparation method and its method of purification of α-cyanoacrylatealkyl monomer, application |
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| CN101468212A (en) * | 2008-05-05 | 2009-07-01 | 孙丽华 | Preparation and application of isobutylcyanoacrylate medical adhesive |
| CN205649337U (en) * | 2016-03-14 | 2016-10-19 | 天津金世制药有限公司 | Oil bath heating intermediate layer pot |
| CN109748819A (en) * | 2019-02-28 | 2019-05-14 | 秦皇岛市科峰医疗器械有限公司 | The preparation method and its method of purification of α-cyanoacrylatealkyl monomer, application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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